More re-post of abstracts on immune system and cognitive function

[Guest guest]

The second one mentions sickness behavior, which

depression is sometimes considered a manifestation

of...

1-Activation of innate immunity in the CNS triggers

neurodegeneration

through a Toll-like receptor 4-dependent pathway.

2-Entry of blood-borne cytokines into the central

nervous system: effects on

cognitive processes.

3-The mannose receptor in the brain.

4-Intrathecal inflammation precedes development of

Alzheimer's disease.

5-Impact of Viral and Bacterial Burden on Cognitive

Impairment in Elderly

Persons With Cardiovascular Diseases

6-Three or more routes for leukocyte migration into

the central nervous

system.

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Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8514-9.

Epub 2003 Jun 24.

Related Articles, Links

Activation of innate immunity in the CNS triggers

neurodegeneration through

a Toll-like receptor 4-dependent pathway.

Lehnardt S, Massillon L, Follett P, Jensen FE, Ratan

R, Rosenberg PA, Volpe

JJ, Vartanian T.

Department of Neurology, Beth Israel Deaconess Medical

Center, Harvard

Medical School, Boston, MA 02115, USA.

Innate immunity is an evolutionarily ancient system

that provides organisms

with immediately available defense mechanisms through

recognition of

pathogen-associated molecular patterns. We show that

in the CNS, specific

activation of innate immunity through a Toll-like

receptor 4

(TLR4)-dependent pathway leads to neurodegeneration.

We identify microglia as the major lipopolysaccharide

(LPS)-responsive cell

in the CNS. TLR4 activation leads to extensive

neuronal death in vitro that

depends on the presence of microglia. LPS leads to

dramatic neuronal loss in

cultures prepared from wild-type mice but does not

induce neuronal injury in

CNS cultures derived from tlr4 mutant mice.

In an in vivo model of neurodegeneration, stimulating

the innate immune

response with LPS converts a subthreshold

hypoxic-ischemic insult from no

discernable neuronal injury to severe axonal and

neuronal loss. In contrast,

animals bearing a loss-of-function mutation in the

tlr4 gene are resistant

to neuronal injury in the same model.

The present study demonstrates a mechanistic link

among innate immunity,

TLRs, and neurodegeneration.

PMID: 12824464 [PubMed - in process]

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Neuroimmunomodulation. 2003;10(6):319-27. Related

Articles, Links

Entry of blood-borne cytokines into the central

nervous system: effects on

cognitive processes.

Banks WA, Farr SA, Morley JE.

GRECC, Veterans Affairs Medical Center, St. Louis and

Saint Louis University

School of Medicine, Division of Geriatrics, Department

of Internal Medicine,

St. Louis, Mo., USA.

Blood-borne cytokines affect many aspects of the

central nervous system

(CNS). One of the more dramatic effects is the

induction of sickness

behavior.

Impairments in learning and memory are an important

component of sickness

behavior and are largely mediated by IL-1. Many

mechanisms have been

proposed by which a cytokine circulating in the blood

can affect functions

within the CNS.

We review here the role one of those mechanisms, that

of transport of

cytokines across the blood-brain barrier (BBB), plays

in induction of the

memory impairments of sickness behavior. We have shown

that the posterior

division of the septum (PDS) plays a key role in

mediating the effects of

interleukin-1alpha (IL-1alpha) on memory.

Furthermore, this effect at the PDS is largely

mediated by circulating

IL-1alpha acting directly at the PDS which, in turn,

depends on the ability

of IL-1alpha to cross the BBB. Copyright 2003 S.

Karger AG, Basel

PMID: 12907838 [PubMed - in process]

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Int Rev Cytol. 2003;226:321-42. Related Articles,

Links

The mannose receptor in the brain.

Regnier-Vigouroux A.

Applied Tumor Virology, AbtF010/INSERM U375, Deutsches

Krebsforschungszentrum, INF 242, 69120, Heidelberg,

Germany.

The mannose receptor is a transmembrane glycoprotein

mainly expressed by

macrophages, that specifically binds to mannosylated

molecules and mediates

their endocytosis. Known ligands of the receptor are

lysosomases and various

pathogens.

Ligand specificity and cellular distribution provide

the mannose receptor

with a very important role in homeostasis and in the

immune response.

_Expression of the mannose receptor has recently been

demonstrated in the

brain. Astrocytes and microglia, two types of glial

cells that can be turned

into immune-competent cells, are the main site of

_expression in vivo and in

vitro.

The mannose receptor mediates in vitro pinocytosis by

astrocytes and

microglia and phagocytosis by microglia. _Expression

and endocytic activities

of the mannose receptor in these cells are regulated

by various cytokines.

Based on our current knowledge on mannose receptor

activities in brain

cells, on its regional and temporal _expression in

that organ, and on its

putative ligands therein, the possible involvement of

the mannose receptor

in brain homeostasis, neuronal functions, and brain

defense is discussed.

PMID: 12921240 [PubMed - in process]

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J Neurol Neurosurg Psychiatry. 2003

Sep;74(9):1200-1205. Related Articles,

Links

Intrathecal inflammation precedes development of

Alzheimer's disease.

Tarkowski E, sen N, Tarkowski A, Blennow K.

Department of Rheumatology, University of Goteborg,

Goteborg, Sweden.

Department of Geriatrics, University of Goteborg.

Department of Clinical

Neurosciences (Section of Neurochemistry), University

of Goteborg and

Department of Clinical Chemistry, University of

Goteborg. Karolinska

Institut, NEUROTEC, Department of Clinical Geriatrics,

Stockholm, Sweden.

OBJECTIVES: To analyse the cerebrospinal fluid (CSF)

values of the

proinflammatory cytokines, interleukin 1beta

(IL1beta), tumour necrosis

factor alpha (TNFalpha), GM-CSF, of the

anti-inflammatory cytokine TGFbeta,

of tau protein, a marker for neurodegeneration, and of

beta amyloid (Abeta),

a protein involved in the formation of senile plaques,

in prospectively

followed up patients with mild cognitive impairment

(MCI).

METHODS: Analyses of CSF levels of TNFalpha, IL1beta,

GM-CSF, TGFbeta,

betaa, and tau protein were performed using ELISA in

56 patients with MCI

who were followed up prospectively and in 25 age

matched, healthy controls.

RESULTS: Patients with MCI displayed significantly

higher levels of TNFalpha

and tau protein and significantly lower levels of

TGFbeta and Abeta compared

with the healthy controls.

After nine months of follow up, 25 patients still

displayed MCI while the

remaining 31 patients had progressed to Alzheimer's

disease (AD). Only MCI

patients who progressed to AD at follow up, showed

significantly higher CSF

levels of TNFalpha than controls. In addition, reduced

CSF-Abeta42 levels

were only found in MCI patients that progressed to AD,

further supporting

the notion that disturbed metabolism of Abeta is an

early finding in AD.

CONCLUSIONS: These results demonstrate increased

production of the

proinflammatory cytokine, TNFalpha and decreased

production of the

anti-inflammatory cytokine TGFbeta in patients with

MCI at risk to develop

AD, suggesting a propensity towards inflammation in

this patient group and

indicating that CNS inflammation is a early hallmark

in the pathogenesis of

AD.

PMID: 12933918 [PubMed - as supplied by publisher]

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Stroke. 2003 Aug 14 [Epub ahead of print]. Related

Articles, Links

Impact of Viral and Bacterial Burden on Cognitive

Impairment in Elderly

Persons With Cardiovascular Diseases.

Strandberg TE, Pitkala KH, Linnavuori KH, Tilvis RS.

Department of Medicine, Geriatric Clinic, and

Department of Virology,

University of Helsinki, Helsinki, Finland.

BACKGROUND AND PURPOSE: Inflammation and infectious

etiology have been

implicated in the pathogenesis of dementia. We sought

to investigate whether

the seropositivity of common infections was associated

with cognitive

function.

METHODS: Viral burden (seropositivity for herpes

simplex virus type 1

[HSV-1], herpes simplex virus type 2 [HSV-2], or

cytomegalovirus [CMV]) and

bacterial burden (Chlamydia pneumoniae and Mycoplasma

pneumoniae) were

related to cognitive status and its impairment among

383 home-dwelling

elderly with cardiovascular diseases (mean age, 80

years). The Mini-Mental

State Examination (MMSE) and its changes and the

Clinical Dementia Rating

(CDR) were used to define cognitive impairment.

RESULTS: At baseline, 0 to 1, 2, and 3 positive titers

toward viruses were

found in 48 (12.5%), 229 (59.8%), and 106 individuals

(27.7%), respectively.

MMSE points decreased with increasing viral burden

(P=0.03). At baseline, 58

individuals (15.1%) had cognitive impairment, which

after adjustments was

significantly associated with seropositivity for 3

viruses (hazard ratio,

2.5; 95% CI, 1.3 to 4.7). MMSE score decreased in 150

(43% of 348) during

12-month follow-up. After adjustment for MMSE score at

baseline and with 0

to 1 seropositivities as reference (1.0), the hazard

ratios were 1.8 (95%

CI, 0.9 to 3.6) and 2.3 (95% CI, 1.1 to 5.0) for 2 and

3 seropositivities,

respectively. The prevalence of possible or definite

dementia according to

CDR also increased with viral burden. No significant

associations were

observed between bacterial burden and cognition.

CONCLUSIONS: Viral pathogen burden of HSV and CMV was

associated with

cognitive impairment in home-dwelling elderly persons

with cardiovascular

diseases. The results need to be tested in larger

databases, but they may

offer a preventable cause of cognitive decline.

PMID: 12920256 [PubMed - as supplied by publisher]

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Nat Rev Immunol. 2003 Jul;3(7):569-81. Related

Articles, Links

Three or more routes for leukocyte migration into the

central nervous

system.

Ransohoff RM, Kivisakk P, Kidd G.

The Mellen Center for Multiple Sclerosis Treatment and

Research, Department

of Neurology, 9500 Euclid Avenue, The Cleveland Clinic

Foundation,

Cleveland, Ohio 44195, USA. ransohr@...

Leukocyte migration into and through tissues is

fundamental to normal

physiology, immunopathology and host defence.

Leukocyte entry into the

central nervous system (CNS) is restricted, in part,

because of the

blood-brain barrier (BBB).

During the past decade, crucial components that are

involved in the process

of leukocyte migration have been identified and

progress has been made in

understanding the mechanisms of neuroinflammatory

reactions.

In this review, present knowledge of the trafficking

determinants that guide

the migration of leukocytes is superimposed onto the

vascular and

compartmental anatomy of the CNS. We discuss three

distinct routes for

leukocytes to enter the CNS and consider how different

populations of

leukocytes use trafficking signals to gain entry.

PMID: 12876559 [PubMed - in process]

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